Potential gene therapy for Sickle cell disease
Sickle cell disease (SCD) is an autosomal recessive disorder caused by mutations in hemoglobin (HBB) that deform red blood cells. A small number of patients have been successfully treated with allogeneic hematopoietic stem cell (HSC) transplantation; however, there are several drawbacks and complications associated with this procedure, including graft vs. host disease and long-term immune suppression. Many of complications could potentially be avoided by the use of autologous HSC transplant, which uses patient cells that have been treated genetically modified to replace defective hemoglobin. In this issue of the Journal of Clinical Investigation , Zulema Romero and colleagues at UCLA investigated the utility of a genetic vector encoding a human hemoglobin gene engineered to impede sickle hemoglobin and prevent the sickling of red blood cells. The vector was used to efficiently transduce bone marrow cells from SCD patients and the transduced cells were successfully transplanted into immunocompromised mice, suggesting that this method could potentially be used to treat SCD.
TITLE: β-globin gene transfer in human bone marrow for sickle cell disease
AUTHOR CONTACT: Zulema Romero
University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Phone: 1-310-794-1884; Fax: 310-267-2774; E-mail: zulemar@ucla.edu
View this article at: http://www.jci.org/articles/view/67930?key=31b284a91ef6d46fc863
Cross-species malaria immunity induced by chemically attenuated parasites
Malaria, a mosquito-born infectious disease, kills over 600,000 people every year. Research has focused on the development of a vaccine to prevent the disease; however, many malaria vaccines targeting parasite antigens have failed because the antigen targets are highly variable. Based on the observation that low-density infections can induce antibody-independent immunity to different malaria strains, Michael Good and colleagues at Griffith University in Australia created a vaccine using blood-stage malaria parasites that were attenuated with a chemical agent that keeps the parasite from multiplying. In this issue of the Journal of Clinical Investigation, they demonstrate that mice inoculated with a single species of attenuated parasite display immunity to multiple malaria species for over 100 days. These data indicate that vaccination with chemically attenuated parasites provides protective immunity and suggest that such vaccines could be used to target human malaria species.
TITLE: Cross-species malaria immunity induced by chemically attenuated parasites
AUTHOR CONTACT: Michael Batzloff
Griffith University, Gold Coast, AUS
Phone: 5552 9434; E-mail: m.batzloff@griffith.edu.au
View this article at: http://www.jci.org/articles/view/66634?key=c4d24ede72f2d54f5147
A potential gene therapy for Mucopolysaccharidosis Type IIIA
Mucopolysaccharidosis Type IIIA (MPSIIIA) is a metabolic disorder in which the body is missing an enzyme that is required to break down long chains of sugars known as glycosaminoglycans. Over time, the glycosaminoglycans collect in the body and cause damage, particularly in the brain. In this issue of the Journal of Clinical Investigation, Fàtima Bosch and colleagues at Universitat Autònoma de Barcelona in Spain developed a form of gene therapy to replace the enzyme that is missing in MPSIIIA. By injecting the replacement gene into the the cerebrospinal fluid that surrounds the brain and spinal cord, Bosch and colleagues found that they could successfully deliver a replacement gene to the brain in mice and dogs. This study demonstrates that gene therapy can be delivered to the brain through the cerebrospinal fluid and suggests that this approach could potentially be used as a therapy for MPSIIIA.
TITLE: Whole body correction of Mucopolysaccharidosis IIIA by intra-cerebrospinal fluid gene therapy
AUTHOR CONTACT: Fàtima Bosch
Universitat Autònoma de Barcelona, Bellaterra, UNK, ESP
Phone: 0034935814182; Fax: 0034935814180; E-mail: fatima.bosch@uab.es
View this article at: http://www.jci.org/articles/view/66778?key=d24b37bc3364f9761834
ALSO IN THIS ISSUE
TITLE: Developmental differences in IFN signaling affect GATA-1s induced megakaryocyte hyperproliferation
AUTHOR CONTACT: Alan Cantor
Children's Hospital Boston/Harvard Medical School, Boston, MA, USA
Phone: 617-919-2026; Fax: 617-730-0222; E-mail: alan.cantor@childrens.harvard.edu
View this article at: http://www.jci.org/articles/view/40609?key=bf056c76f25f2f38ba80
TITLE: Inactivation of specific beta-cell transcription factors in Type 2 diabetes
AUTHOR CONTACT: Roland Stein
Vanderbilt University Medical Center, Nashville, TN, USA
Phone: 615-322-7027; Fax: 615-322-7236; E-mail: roland.stein@vanderbilt.edu
View this article at: http://www.jci.org/articles/view/65390?key=10e9ec4fdc34c0b7fedb
TITLE: Colon cancer progression is driven by APEX1-mediated up-regulation of Jagged
AUTHOR CONTACT: Ho Jin You
Chosun University School of Medicine, Gwangju, KOR
Phone: 82-62-230-6337; Fax: 82-62-230-6337; E-mail: hjyou@chosun.ac.kr
View this article at: http://www.jci.org/articles/view/65521?key=e4dab4c22c7ba7ac357f
TITLE: Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis
AUTHOR CONTACT: Christian Kupatt
Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, DEU
Phone: +49-89-7095-6092; Fax: +49-89-7095-6075; E-mail: christian.kupatt@med.uni-muenchen.de
View this article at: http://www.jci.org/articles/view/66549?key=72b1105b45c139d4740b
TITLE: Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis
AUTHOR CONTACT: Lorenzo Ferri
MUHC, Montreal, PQ, CAN
Phone: 514-934-1934 ext. 44327; Fax: 514-398-6769; E-mail: Lorenzo.ferri@mcgill.ca
View this article at: http://www.jci.org/articles/view/67484?key=c5d09b064fa708677328
TITLE: Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes
AUTHOR CONTACT: Sylvia Knapp
Medical University Vienna, Vienna, AUT
Phone: +43-1-40400-5139; Fax: +43-1-40400-5167; E-mail: sylvia.knapp@meduniwien.ac.at
View this article at: http://www.jci.org/articles/view/67911?key=3b51a00fcbe441d92d74
TITLE: Gray platelet syndrome and defrective thrombo-inflammation in Nbeal2-deficient mice
AUTHOR CONTACT: Bernhard Nieswandt
University Hospital Würzburg and Rudolf Virchow Center, Würzburg, , DEU
Phone: +49 931 31 80405; Fax: +49 931 201 48123; E-mail: bernhard.nieswandt@virchow.uni-wuerzburg.de
View this article at: http://www.jci.org/articles/view/69210?key=0fc85302255cce6a5803
Journal
Journal of Clinical Investigation